Hitherto, it has been well known through patent publications and general scientific literature that an active vitamin D3 plays an extremely important role as a substance controlling the metabolism of calcium, phosphates, etc., in a living body. Further, it is widely known that various kinds of vitamin D derivatives have been used as treating agents for metabolic disorders of vitamin D including osteoporosis and rickets.
Furthermore, there is a report that the fact in which vitamin D3 has calcium controlling activity and other various kinds of biological activities found in vitamin D3 is considered attributable to the occurrence of various kinds of selectivity based on the difference between a binding affinity to a vitamin D receptor and that to a vitamin D binding protein.
As a known 2-position substituted vitamin D3 derivative, 1,25-dihydroxyvitamin D3 derivatives, which have a hydroxyl group of α-configuration at the 1-position and a substituent (no substituent, a C1 to C6 linear alkyl group substituted with a hydroxyl group at the terminal, a C1 to C6 linear alkyloxy group substituted with a hydroxyl group at the terminal, a C1 to C5 alkenyl group or a hydroxyl group) of β-configuration at the 2-position, have been reported [Kobayashi, et al., 116th (1996) Congress of The Pharmaceutical Society of Japan, Abstract 3, 88].
Further, 1,25-dihydroxyvitamin D3 derivatives having a hydroxyl group of α-configuration at the 1-position and a substituent (3-hydroxypropyl group or 3-fluoropropyl group) of α-configuration at the 2-position have been reported [Posner, G. H., J. Org. Chem., 60, 4617 (1995)].
Furthermore, there is a report of a study concerning other stereoisomers based on asymmetric carbons at the 1-, 2- and 3-positions of 1,25-dihydroxy-2-methylvitamin D3 derivatives (Maki, et al., 116th (1996) Congress of The Pharmaceutical Society of Japan, Abstract 2, 9).
However, no stereoisomer (20S-form) that is different from natural products regarding the configuration of the carbon atom at the 20-position in 1,25-dihydroxy-2-methylvitamin D3 derivatives being known, there in no information what kinds of influences does the configuration of the carbon atom at the 20-position exert upon a binding affinity to a vitamin D receptor or to a vitamin D bonding protein, or upon other various kinds of above-mentioned biological activities.
In addition, although methods for producing 2-position substituted vitamin D3 derivatives are also described in the above reports, only isomers having specific combinations of configurations of the 1-, 2- and 3-asymmetric carbons among all the combinations of the configurations are disclosed in these reports, and no method for efficiently producing an isomer having an arbitrary combination of the configurations is reported.
Recently, a new method through which an active type of vitamin D3 is synthesized by reacting an exo-methylene compound expressed by the following general formula (II′),                 (wherein X is a bromine atom or an iodine atom) with an ene-yne compound expressed by the following general formula (III′), [wherein R3 and R4 are each independently a hydrogen atom or a tri(C1 to C7 hydrocarbon)silyl group] has been reported [Trost, B. M., J. Am. Chem. Soc., 114, 9836 (1992)]. However, no one has reported that an ene-yne compound having a substituent such as methyl group at the 4-position is used as the above ene-yne compound.        